In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 4_suppl ( 2017-02-01), p. 61-61
Abstract:
61 Background: Chromosomal instability (CIN), defined as cell to cell variation in copy number, is a feature of solid tumors that has been shown in experimental systems to result in aneuploidy, DNA damage, changes in gene expression, and genetically heterogeneous cell populations. In esophageal adenocarcinoma, chromosome 17 (Chr17) aneusomy is associated with heterogeneous HER2 amplification, a marker of poor prognosis (Yoon et al., J Clin Oncol 2012), but the association between CIN, HER2 amplification and clinical outcome has not been well studied. Methods: We retrospectively analyzed individual cell Chr17 centromere counts in 348 gastroesophageal adenocarcinomas that were tested for HER2 amplification. As an estimate of Chr17 CIN (CIN-17), we calculated the percentage of cells with centromere counts differing from the mode (modal centromere deviation, MCD, Roylance et al. Cancer Epidemiol Biomarkers Prev, 2011). We analyzed the association of CIN-17 with Chr17 aneusomy, HER2 amplification, pathologic tumor characteristics and clinical outcome. Results: Using pre-established cutoffs, we found CIN-17 (MCD 〉 30%) in 45% (158/348) and extreme CIN-17 (MCD 〉 45%) in 28% (99/348) of cases. Compared to CIN-17 negative tumors, CIN-17 positive tumors were more likely to be polysomic (77% vs 0.5%, P 〈 0.001) and Lauren intestinal type (84% vs 70%, P = 0.005). HER2 amplification was detected in 23% (80/348) of tumors, but there was no association with CIN-17 (P = 0.493). In patients who received pharmacologic therapy (n = 77), there was a 58% reduction in overall mortality associated with extreme CIN-17 (HR = 0.42, 0.25-0.72) independent of age, stage and addition of trastuzumab. Addition of trastuzumab to pharmacologic therapy showed a trend toward improved clinical outcome only in the subgroup without extreme CIN (n = 50, HR = 0.37, 0.13-1.06). CIN-17 was not associated with differences in patient survival after surgical resection. Conclusions: In this retrospective study, extreme CIN-17 was a favorable prognostic factor in patients who receive chemotherapy but could impair response to trastuzumab. These findings warrant further study.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.4_suppl.61
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
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